1. Field of the Invention
The invention relates to the discovery of mutant alleles at the glucokinase gene locus on the short arm of human chromosome 7. The invention relates as well to the correlation between these alleles and certain forms of non-insulin dependent diabetes mellitus. In particular, the invention provides methods for detecting subjects with a propensity to develop certain forms of diabetes by virtue of their possession of mutant glucokinase alleles. The invention further provides methods for determining the molecular mechanisms associated with defective glucokinase as these mechanisms relate to substrate/ligand binding by the enzyme.
2. Description of the Related Art
Non-Insulin Dependent Diabetes Mellitus
Non-insulin-dependent or Type 2 diabetes mellitus (NIDDM) is a major public health disorder of glucose homeostasis affecting about 5-7% of the general population. Clinically, NIDDM is a heterogenous disorder characterized by chronic hyperglycemia leading to progressive micro- and macrovascular lesions in the cardiovascular, renal and visual systems as well as diabetic neuropathy. The causes of the fasting hyperglycemia and/or glucose intolerance associated with this form of diabetes are not well understood. Unfortunately, the disease is associated with early morbidity and mortality.
Subtypes of the disease can be identified based at least to some degree on the time of onset of the symptoms. The principal type of NIDDM occurs at a later time of onset, typically at midlife. Early-onset NIDDM or maturity-onset diabetes of the young (MODY) shares many features with the more common form(s) of NIDDM but onset occurs in early life.